The association between vaginal bacterial composition and miscarriage: a nested case-control study

Study information

Reviewed Marked as Reviewed by Fatima on 2021/10/20

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

31573753

DOI Digital object identifier for electronic documents.

10.1111/1471-0528.15972

URI

Authors

Al-Memar M, Bobdiwala S, Fourie H, Mannino R, Lee YS, Smith A, Marchesi JR, Timmerman D, Bourne T, Bennett PR, MacIntyre DA

Journal

BJOG : an international journal of obstetrics and gynaecology

Year

2020

Keywords:

First trimester miscarriage, second trimester miscarriage, vaginal bacteria, vaginal microbiome

OBJECTIVE: To characterise vaginal bacterial composition in early pregnancy and investigate its relationship with first and second trimester miscarriages. DESIGN: Nested case-control study. SETTING: Queen Charlotte's and Chelsea Hospital, Imperial College Healthcare NHS Trust, London. POPULATION: 161 pregnancies: 64 resulting in first trimester miscarriage, 14 in second trimester miscarriage and 83 term pregnancies. METHODS: Prospective profiling and comparison of vaginal bacteria composition using 16S rRNA gene-based metataxonomics from 5 weeks' gestation in pregnancies ending in miscarriage or uncomplicated term deliveries matched for age, gestation and body mass index. MAIN OUTCOME MEASURES: Relative vaginal bacteria abundance, diversity and richness. Pregnancy outcomes defined as first or second trimester miscarriage, or uncomplicated term delivery. RESULTS: First trimester miscarriage associated with reduced prevalence of Lactobacillus spp.-dominated vaginal microbiota classified using hierarchical clustering analysis (65.6 versus 87.7%; P = 0.005), higher alpha diversity (mean Inverse Simpson Index 2.5 [95% confidence interval 1.8-3.0] versus 1.5 [1.3-1.7], P = 0.003) and higher richness 25.1 (18.5-31.7) versus 16.7 (13.4-20), P = 0.017), compared with viable pregnancies. This was independent of vaginal bleeding and observable before first trimester miscarriage diagnosis (P = 0.015). Incomplete/complete miscarriage associated with higher proportions of Lactobacillus spp.-depleted communities compared with missed miscarriage. Early pregnancy vaginal bacterial stability was similar between miscarriage and term pregnancies. CONCLUSIONS: These findings associate the bacterial component of vaginal microbiota with first trimester miscarriage and indicate suboptimal community composition is established in early pregnancy. While further studies are required to elucidate the mechanism, vaginal bacterial composition may represent a modifiable risk factor for first trimester miscarriage. TWEETABLE ABSTRACT: Vaginal bacterial composition in first trimester miscarriage is associated with reduced Lactobacillus spp. abundance and is independent of vaginal bleeding.

Experiment 1

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Reviewed Marked as Reviewed by Fatima on 2021/10/20

Curated date: 2021/10/14

Curator: Titas

Revision editor(s): Fatima, Titas, WikiWorks

Subjects

Location of subjects: United Kingdom

Host species Species from which microbiome was sampled (if applicable): Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Posterior fornix of vagina Pars posterior fornicis vaginae,Posterior fornix,Posterior part of fornix of vagina,Posterior fornix of vagina

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: spontaneous abortion Abortion, spontaneous,spontaneous abortion

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Viable control pregnancy
Group 1 name Corresponds to the case (exposed) group for case-control studies: First or second-trimester miscarriage
Group 0 sample size Number of subjects in the control (unexposed) group: 81
Group 1 sample size Number of subjects in the case (exposed) group: 77

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V1-V2

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Statistical test: Chi-Square

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05
Matched on Factors on which subjects have been matched on in a case-control study: age, body mass index, gestational age

Alpha Diversity

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa: increased
Richness Number of species: increased

Signature 1

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Source: Figure 2A

Description:

Abundance in Group 1: decreased abundance in First or second-trimester miscarriage

NCBI	Quality Control	Links
Lactobacillus sp.

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Experiment 2

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Curated date: 2021/10/14

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Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies: First trimester miscarriage
Group 1 sample size Number of subjects in the case (exposed) group: 64

Sequencing type: Not specified

Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Not specified

Statistical test: Not specified

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): Not specified
Matched on Factors on which subjects have been matched on in a case-control study: Not specified

Signature 1

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Source: 2D

Description:

Abundance in Group 1: decreased abundance in First trimester miscarriage

NCBI	Quality Control	Links
Lactobacillus sp.

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Signature 2

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Source: Figure 2D + interpretation

Description: Samples deplete of Lactobacillus spp. display increased richness and diversity and colonization by potential pathogens.

Abundance in Group 1: increased abundance in First trimester miscarriage

NCBI	Quality Control	Links
Prevotella sp.
Streptococcus
Peptoniphilus
Ureaplasma
Dialister

Revision editor(s): Titas

Experiment 3

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Curated date: 2021/10/14

Curator: Titas

Revision editor(s): LGeistlinger, Titas, WikiWorks

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: missed miscarriage
Group 1 name Corresponds to the case (exposed) group for case-control studies: complete/incomplete miscarriage
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: A missed miscarriage is when a baby has died in the womb, but the mother hasn't had any symptoms, such as bleeding or pain.

A complete miscarriage has taken place when all the pregnancy tissue has left your uterus.